The Washington Metropolitan Consortium, under the leadership of Principal Investigator Mary Young, MD, has established a stable cohort of representative HIV infected and uninfected women during the initial funding cycle of the Women's Interagency HIV Study (WIHS). Enrollment figures exceeded the planned enrollment by 7 percent, of which 85 percent have been retained. This cohort has served as the basis for collaborative studies investigating hypotheses that address issues in women's health, HIV disease progression, gynecologic, behavioural and laboratory evaluations of both HIV infected and uninfected women. We propose maintaining this cohort to maximize our ability to address core hypotheses in a prospective fashion. We propose expanding the original core hypotheses to address research questions that have been raised in light of major advances in our understanding of the pathophysiology of HIV and advances in therapeutic treatment options. This will involve maintaining existing collaborations and expanding beyond WIHS to basic science researchers with specific expertise through alternative funding mechanism. Thus, we will maximize access to valuable repository specimens that have been acquired during the initial studies and will be maintained and expanded during WIHS II. This collaborative study has succeeded at both the national and local level because of a high level of committment to the participants, as evidenced by their inclusion in all aspects of protocol development and evaluation. This cohort is now poised to make a significant contribution to women's health and to our understanding of viral-host interactions, and specifically HIV viral pathogenesis. Issues related to transmission, infection and gynecologic health are being addressed and important interactions between behaviours, health care utilization, risk of infection and disease progression are being studied. The new natural history of HIV in the era of highly active antiretrovirals can now be defined. In summary, maintenance of this well characterized, representative cohort of women and its extensive repository of specimens allows for an expansion of our knowledge, not only of HIV but of issues in women's health also.